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Thrombopoietic-mesenchymal interaction that may facilitate both endochondral ossification and platelet maturation via CCN2.

Sumiyoshi K, Kubota S, Furuta RA, Yasui K, Aoyama E, Kawaki H, Kawata K, Ohgawara T, Yamashiro T, Takigawa M - J Cell Commun Signal (2009)

Bottom Line: In this study, we initially pursued the possible origin of the CCN2 in platelets.As suspected, CCN2 production by HCS-2/8 was significantly enhanced by the conditioned medium.We further confirmed that human platelets were able to absorb/uptake exogenous CCN2 in vitro.

View Article: PubMed Central - PubMed

ABSTRACT
CCN2 plays a central role in the development and growth of mesenchymal tissue and promotes the regeneration of bone and cartilage in vivo. Of note, abundant CCN2 is contained in platelets, which is thought to play an important role in the tissue regeneration process. In this study, we initially pursued the possible origin of the CCN2 in platelets. First, we examined if the CCN2 in platelets was produced by megakaryocyte progenitors during differentiation. Unexpectedly, neither megakaryocytic CMK cells nor megakaryocytes that had differentiated from human haemopoietic stem cells in culture showed any detectable CCN2 gene expression or protein production. Together with the fact that no appreciable CCN2 was detected in megakaryocytes in vivo, these results suggest that megakaryocytes themselves do not produce CCN2. Next, we suspected that mesenchymal cells situated around megakaryocytes in the bone marrow were stimulated by the latter to produce CCN2, which was then taken up by platelets. To evaluate this hypothesis, we cultured human chondrocytic HCS-2/8 cells with medium conditioned by differentiating megakaryocyte cultures, and then monitored the production of CCN2 by the cells. As suspected, CCN2 production by HCS-2/8 was significantly enhanced by the conditioned medium. We further confirmed that human platelets were able to absorb/uptake exogenous CCN2 in vitro. These findings indicate that megakaryocytes secrete some unknown soluble factor(s) during differentiation, which factor stimulates the mesenchymal cells to produce CCN2 for uptake by the platelets. We also consider that, during bone growth, such thrombopoietic-mesenchymal interaction may contribute to the hypertrophic chondrocyte-specific accumulation of CCN2 that conducts endochondral ossification.

No MeSH data available.


Related in: MedlinePlus

a Immunostaining of CCN2 produced by chondrocytes in the hypertrophic layer of mouse growth plate near the bone marrow. Note that cells on the bone marrow side accumulate more CCN2 than those on the inner side. b Schematic representation of possible thrombopoietic-mesenchymal interaction around the growth plate-bone marrow boundary. We hypothesize that megakaryocyte progenitors secrete some unknown soluble factor during differentiation, which factor stimulates the chondrocytes facing the bone marrow to produce CCN2. During bone growth, this interaction contributes to the accumulation of CCN2, not only in platelets, but also in the hypertrophic chondrocytes that conduct proper endochondral ossification. Abbreviations: R resting chondrocyte; G growing chondrocyte; Pre-H pre-hypertrophic chondrocyte; H hypertrophic chondrocyte; Meg megakaryocyte
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Fig7: a Immunostaining of CCN2 produced by chondrocytes in the hypertrophic layer of mouse growth plate near the bone marrow. Note that cells on the bone marrow side accumulate more CCN2 than those on the inner side. b Schematic representation of possible thrombopoietic-mesenchymal interaction around the growth plate-bone marrow boundary. We hypothesize that megakaryocyte progenitors secrete some unknown soluble factor during differentiation, which factor stimulates the chondrocytes facing the bone marrow to produce CCN2. During bone growth, this interaction contributes to the accumulation of CCN2, not only in platelets, but also in the hypertrophic chondrocytes that conduct proper endochondral ossification. Abbreviations: R resting chondrocyte; G growing chondrocyte; Pre-H pre-hypertrophic chondrocyte; H hypertrophic chondrocyte; Meg megakaryocyte

Mentions: It is known that CCN2 is mainly produced by hypertrophic chondrocytes facing, or adjacent to bone marrow in the growth plate (Takigawa et al. 2003), which is consistent with our present findings. To confirm this point, we reevaluated the distribution of CCN2 in the mouse growth plate and found that CCN2 was abundantly produced by late hypertrophic chondrocytes near the bone marrow, whereas a relatively limited amount was detected in the inner side (Fig. 7a). These results suggest a possible haemopoietic-mesenchymal interaction that enables the enhanced CCN2 production by hypertrophic chondrocytes.Fig. 7


Thrombopoietic-mesenchymal interaction that may facilitate both endochondral ossification and platelet maturation via CCN2.

Sumiyoshi K, Kubota S, Furuta RA, Yasui K, Aoyama E, Kawaki H, Kawata K, Ohgawara T, Yamashiro T, Takigawa M - J Cell Commun Signal (2009)

a Immunostaining of CCN2 produced by chondrocytes in the hypertrophic layer of mouse growth plate near the bone marrow. Note that cells on the bone marrow side accumulate more CCN2 than those on the inner side. b Schematic representation of possible thrombopoietic-mesenchymal interaction around the growth plate-bone marrow boundary. We hypothesize that megakaryocyte progenitors secrete some unknown soluble factor during differentiation, which factor stimulates the chondrocytes facing the bone marrow to produce CCN2. During bone growth, this interaction contributes to the accumulation of CCN2, not only in platelets, but also in the hypertrophic chondrocytes that conduct proper endochondral ossification. Abbreviations: R resting chondrocyte; G growing chondrocyte; Pre-H pre-hypertrophic chondrocyte; H hypertrophic chondrocyte; Meg megakaryocyte
© Copyright Policy
Related In: Results  -  Collection

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Fig7: a Immunostaining of CCN2 produced by chondrocytes in the hypertrophic layer of mouse growth plate near the bone marrow. Note that cells on the bone marrow side accumulate more CCN2 than those on the inner side. b Schematic representation of possible thrombopoietic-mesenchymal interaction around the growth plate-bone marrow boundary. We hypothesize that megakaryocyte progenitors secrete some unknown soluble factor during differentiation, which factor stimulates the chondrocytes facing the bone marrow to produce CCN2. During bone growth, this interaction contributes to the accumulation of CCN2, not only in platelets, but also in the hypertrophic chondrocytes that conduct proper endochondral ossification. Abbreviations: R resting chondrocyte; G growing chondrocyte; Pre-H pre-hypertrophic chondrocyte; H hypertrophic chondrocyte; Meg megakaryocyte
Mentions: It is known that CCN2 is mainly produced by hypertrophic chondrocytes facing, or adjacent to bone marrow in the growth plate (Takigawa et al. 2003), which is consistent with our present findings. To confirm this point, we reevaluated the distribution of CCN2 in the mouse growth plate and found that CCN2 was abundantly produced by late hypertrophic chondrocytes near the bone marrow, whereas a relatively limited amount was detected in the inner side (Fig. 7a). These results suggest a possible haemopoietic-mesenchymal interaction that enables the enhanced CCN2 production by hypertrophic chondrocytes.Fig. 7

Bottom Line: In this study, we initially pursued the possible origin of the CCN2 in platelets.As suspected, CCN2 production by HCS-2/8 was significantly enhanced by the conditioned medium.We further confirmed that human platelets were able to absorb/uptake exogenous CCN2 in vitro.

View Article: PubMed Central - PubMed

ABSTRACT
CCN2 plays a central role in the development and growth of mesenchymal tissue and promotes the regeneration of bone and cartilage in vivo. Of note, abundant CCN2 is contained in platelets, which is thought to play an important role in the tissue regeneration process. In this study, we initially pursued the possible origin of the CCN2 in platelets. First, we examined if the CCN2 in platelets was produced by megakaryocyte progenitors during differentiation. Unexpectedly, neither megakaryocytic CMK cells nor megakaryocytes that had differentiated from human haemopoietic stem cells in culture showed any detectable CCN2 gene expression or protein production. Together with the fact that no appreciable CCN2 was detected in megakaryocytes in vivo, these results suggest that megakaryocytes themselves do not produce CCN2. Next, we suspected that mesenchymal cells situated around megakaryocytes in the bone marrow were stimulated by the latter to produce CCN2, which was then taken up by platelets. To evaluate this hypothesis, we cultured human chondrocytic HCS-2/8 cells with medium conditioned by differentiating megakaryocyte cultures, and then monitored the production of CCN2 by the cells. As suspected, CCN2 production by HCS-2/8 was significantly enhanced by the conditioned medium. We further confirmed that human platelets were able to absorb/uptake exogenous CCN2 in vitro. These findings indicate that megakaryocytes secrete some unknown soluble factor(s) during differentiation, which factor stimulates the mesenchymal cells to produce CCN2 for uptake by the platelets. We also consider that, during bone growth, such thrombopoietic-mesenchymal interaction may contribute to the hypertrophic chondrocyte-specific accumulation of CCN2 that conducts endochondral ossification.

No MeSH data available.


Related in: MedlinePlus